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Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study

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Abstract
Abstract
Purpose: Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (Exon20ins) mutations exhibits inherent resistance to approved tyrosine kinase inhibitors. Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, binds to each receptor's extracellular domain, bypassing resistance at the tyrosine kinase inhibitor binding site.

Methods: CHRYSALIS is a phase I, open-label, dose-escalation, and dose-expansion study, which included a population with EGFR Exon20ins NSCLC. The primary end points were dose-limiting toxicity and overall response rate. We report findings from the postplatinum EGFR Exon20ins NSCLC population treated at the recommended phase II dose of 1,050 mg amivantamab (1,400 mg, ≥ 80 kg) given once weekly for the first 4 weeks and then once every 2 weeks starting at week 5.

Results: In the efficacy population (n = 81), the median age was 62 years (range, 42-84 years); 40 patients (49%) were Asian, and the median number of previous lines of therapy was two (range, 1-7). The overall response rate was 40% (95% CI, 29 to 51), including three complete responses, with a median duration of response of 11.1 months (95% CI, 6.9 to not reached). The median progression-free survival was 8.3 months (95% CI, 6.5 to 10.9). In the safety population (n = 114), the most common adverse events were rash in 98 patients (86%), infusion-related reactions in 75 (66%), and paronychia in 51 (45%). The most common grade 3-4 adverse events were hypokalemia in six patients (5%) and rash, pulmonary embolism, diarrhea, and neutropenia in four (4%) each. Treatment-related dose reductions and discontinuations were reported in 13% and 4% of patients, respectively.

Conclusion: Amivantamab, via its novel mechanism of action, yielded robust and durable responses with tolerable safety in patients with EGFR Exon20ins mutations after progression on platinum-based chemotherapy.

Trial registration: ClinicalTrials.gov NCT02609776.
Author(s)
김상위Amy RoshakByoung Chul ChoCatherine A ShuDawn MillingtonDong-Wan KimEric B HauraJames Chih-Hsin YangJi-Youn HanJohn XieJong-Seok LeeJose TrigoJoshua C CurtinJoshua M BaumlKaren L ReckampKeunchil ParkKi Hyeong LeeKoichi GotoMatthew G KrebsMeena ThayuNahor Haddish-BerhaneNata
Issued Date
2021
Type
Article
Keyword
AdultAgedAged80 and overAntibodiesBispecific - administration & dosageAntibodiesBispecific - adverse effectsAntibodiesBispecific - pharmacokineticsAntineoplastic AgentsImmunological - administration & dosageAntineoplastic AgentsImmunological - adverse effectsAntineoplastic AgentsImmunological - pharmacokineticsCarcinomaNon-Small-Cell Lung - drug therapyCarcinomaNon-Small-Cell Lung - geneticsCarcinomaNon-Small-Cell Lung - secondaryDiarrhea - chemically inducedDisease ProgressionDrug Eruptions - etiologyErbB Receptors - genetics ExonsFemaleHumansHypokalemia - chemically inducedInjection Site Reaction - etiologyLung Neoplasms - drug therapyLung Neoplasms - geneticsLung Neoplasms - pathologyMaleMiddle AgedMutagenesisInsertionalNeutropenia - chemically inducedOrganoplatinum Compounds - therapeutic useParonychia - chemically inducedProgression-Free SurvivalPulmonary Embolism - chemically inducedRetreatment
DOI
10.1200/JCO.21.00662
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8434
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2557548781&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Amivantamab%20in%20EGFR%20Exon%2020%20Insertion-Mutated%20Non-Small-Cell%20Lung%20Cancer%20Progressing%20on%20Platinum%20Chemotherapy:%20Initial%20Results%20From%20the%20CHRYSALIS%20Phase%20I%20Study&offset=0&pcAvailability=true
Publisher
JOURNAL OF CLINICAL ONCOLOGY
Location
미국
Language
영어
ISSN
0732-183X
Citation Volume
39
Citation Number
30
Citation Start Page
3391
Citation End Page
3402
Appears in Collections:
Medicine > Medicine
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